FcγRIIB receptor-mediated apoptosis in macrophages through interplay of cadmium sulfide nanomaterials and protein corona

Ecotoxicol Environ Saf. 2018 Nov 30:164:140-148. doi: 10.1016/j.ecoenv.2018.08.025. Epub 2018 Aug 11.

Abstract

Humans are likely exposed to cadmium sulfide nanomaterials (CdS NMs) due to the increasing environmental release and in vivo application of these materials, which tend to accumulate and cause toxic effects in human lungs, particularly by interrupting the physiological functions of macrophage cells. Here, we showed that protein corona played an essential role in determining cellular uptake and cytotoxicity of CdS NMs in macrophages. Protein-coated CdS NMs enhanced the expression of FcγRIIB receptors on the cell surface, and the interaction between this receptors and proteins inhibited cellular uptake of CdS NMs while triggering cell apoptosis via the AKT/Caspase 3 signaling pathway. Cytotoxicity of CdS NMs was greatly alleviated by coating the nanomaterials with polyethylene glycol (PEG), because PEG decreased the adsorption of proteins that interact with the FcγRIIB receptors on cell surface. Overall, our research demonstrated that surface modification, particularly protein association, significantly affected cellular response to CdS NMs, and cellular uptake may not be an appropriate parameter for predicting the toxic effects of these nanomaterials in human lungs.

Keywords: Apoptosis; Cadmium sulfide nanomaterials; Cellular uptake; FcγRIIB receptors; Macrophages; Protein corona.

MeSH terms

  • Apoptosis / drug effects*
  • Cadmium Compounds / toxicity*
  • Caspase 3 / metabolism
  • Cell Line
  • Humans
  • Lung / drug effects
  • Lung / metabolism
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Nanostructures / toxicity*
  • Polyethylene Glycols / chemistry
  • Protein Corona / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptors, IgG / metabolism*
  • Signal Transduction
  • Sulfides / toxicity*

Substances

  • Cadmium Compounds
  • FCGR2B protein, human
  • Protein Corona
  • Receptors, IgG
  • Sulfides
  • cadmium sulfide
  • Polyethylene Glycols
  • Proto-Oncogene Proteins c-akt
  • CASP3 protein, human
  • Caspase 3